Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses.
Amino Acid Motifs
Animals
Antibodies, Viral
/ immunology
Broadly Neutralizing Antibodies
/ immunology
COVID-19
/ genetics
COVID-19 Vaccines
/ genetics
Female
Humans
Male
Mice
Mice, Inbred BALB C
Polysaccharides
/ genetics
Protein Domains
Severe acute respiratory syndrome-related coronavirus
/ genetics
SARS-CoV-2
/ genetics
Spike Glycoprotein, Coronavirus
/ genetics
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
06 12 2021
06 12 2021
Historique:
received:
09
05
2021
revised:
24
08
2021
accepted:
22
09
2021
entrez:
8
10
2021
pubmed:
9
10
2021
medline:
21
10
2021
Statut:
ppublish
Résumé
Broadly protective vaccines against SARS-related coronaviruses that may cause future outbreaks are urgently needed. The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. These results have implications for the design of SARS-like virus vaccines.
Identifiants
pubmed: 34623376
pii: 212688
doi: 10.1084/jem.20211003
pmc: PMC8641255
pii:
doi:
Substances chimiques
Antibodies, Viral
0
Broadly Neutralizing Antibodies
0
COVID-19 Vaccines
0
Polysaccharides
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japan Society for the Promotion of Science
ID : JP19H01028
Organisme : Japan Agency for Medical Research and Development
ID : JP20fk0108104
Informations de copyright
© 2021 Shinnakasu et al.
Déclaration de conflit d'intérêts
Disclosures: R. Shinnakasu, S. Sakakibara, and T. Kurosaki reported a patent to "glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses" pending. N. Sax and K. Yamashita reported personal fees from KOTAI Biotechnologies, Inc. outside the submitted work. No other disclosures were reported.
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